Over 25 years since recognition of the HIV pandemic, the HIV-infected subjects have moved toward older ages due to improvements in antiretroviral therapy. Non-AIDS-defining co-morbidities such as atherosclerosis, neurocognitive decline and osteoporosis occur despite viral suppression, presenting intriguing similarities to old age. Highly active anti-retroviral therapy (HAART) has reduced mortality in the last decade though mortality rate in HIV-infected African Americans is higher as compared to Hispanic, Asians or whites. Although the reasons for the disparities are poorly understood, psychosocial stress is one factor that may account for the poorer clinical outcomes in HIV-infected subjects in African Americans compared to Whites. The goal of this proposal is to test the hypothesis that immune perturbations, namely immune activation and inflammation, in HIV-infected subjects will contribute to early immune senescence and that these perturbations are enhanced in African Americans compared to white HIV-infected subjects contributing to early senescence and faster HIV disease progression. This project will also test the hypothesis that psychosocial stress may account for the increased activation, inflammation and senescence in African Americans compared to white HIV infected subjects as well as more rapid disease progression. We will conduct this study in specimens from the Rush CEDHA Repository of the Research Core. Novel to this application we will study whether innate immune activation contributes to immune senescence and use telomere shortening as a measure of senescence. We will evaluate immune perturbations, immune activation (HLADR+ CD38+ expression on CD4 and CDS T cells), innate cell activation (soluble CD14, type 1 intereferon-alpha and beta), inflammation (pro- and anti) TNF-alpha, IL-6, IL-10) and immune senescence (defined as CD28-CD57+ expression on CD4 and CDS T cells and telomere length) in age matched HIV infected and uninfected individuals (age 50-60) and older HIV-uninfected (age >70), a unique population accessible via the Research Core of Rush CEDHA. Impact of race and psychosocial stress on immune perturbation will be evaluated in HIV infected subjects. This project has a cross discipline expertise, from leading clinicians in the HIV/AIDS field, immunologists, neuropsychologist and bio-statiscian for successful implementation of the aims and objectives of this study.